chr11-62998959-A-T

Position:

• chr11-62998959-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004254.4(SLC22A8):​c.723T>A​(p.Thr241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,400 control chromosomes in the GnomAD database, including 25,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2219 hom., cov: 33)
  • Exomes 𝑓: 0.17 (23693 hom.)
• Consequence: SLC22A8 NM_004254.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.53

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-4.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A8	NM_004254.4	c.723T>A	p.Thr241=	synonymous_variant	5/11	ENST00000336232.7	NP_004245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7	c.723T>A	p.Thr241=	synonymous_variant	5/11	1	NM_004254.4	ENSP00000337335	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23467 AN: 152164 Hom.: 2214 Cov.: 33

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.193 AC: 48385 AN: 251080 Hom.: 5404 AF XY: 0.190 AC XY: 25717 AN XY: 135672

Gnomad AFR exome AF: 0.0609

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.174 AC: 253864 AN: 1461118 Hom.: 23693 Cov.: 32 AF XY: 0.175 AC XY: 126861 AN XY: 726754

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.165

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.154 AC: 23481 AN: 152282 Hom.: 2219 Cov.: 33 AF XY: 0.157 AC XY: 11707 AN XY: 74450

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.176

Alfa AF: 0.160 Hom.: 1606

Bravo AF: 0.163

Asia WGS AF: 0.206 AC: 716 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2276299; hg19: chr11-62766431; COSMIC: COSV60325283; COSMIC: COSV60325283;